An ion-processing device operating as an ion trap is useful in mass spectrometry and other applications requiring the manipulation and control of ions, particularly ionized species of sample materials under investigation. Such an ion processing device may be formed by a three-dimensional (3-D) or two-dimensional (2-D, or “linear”) arrangement of electrodes. In the case of a 3-D ion trap, the electrode set typically includes two opposing end caps spaced from each other along a central (z) axis, and a ring electrode symmetrically positioned between the end caps. The ring electrode has a cross-section annularly swept about the z-axis at a radial distance on a radial (r) axis orthogonal to the z-axis. In the case of a 2-D ion trap, the electrode set typically includes four electrodes coaxially arranged about a central (z) axis and elongated in the direction of the z-axis. Typically, each elongated electrode of the 2-D ion trap is positioned in an x-y plane orthogonal to the central z-axis at a radial distance (x or y) from the central z-axis, and typically runs parallel to the other electrodes of the same set. In both of the 3-D and 2-D cases, the inside surfaces of the electrodes are typically hyperbolic, with apices facing inwardly toward the 3-D center or 2-D central axis, to produce a pure quadrupolar electric field. In the 2-D case, however, the elongated electrodes may be cylindrical rods that approximate the ideal hyperbolic profiles. In both of the 3-D and 2-D cases, the resulting arrangement of electrodes defines an interior space generally bounded by the inside surfaces of the electrodes. In the 2-D case, the interior space is axially elongated along the z-axis as a result of the elongated dimensions of the electrodes along this same axis.
In operation, ions may be introduced, trapped, stored, isolated, fragmented, and subjected to various reactions in the interior space of the ion trap, and may be ejected from the interior space for detection. In the 3-D case, the excursions of ions in 3-space (resolved, for example, by cylindrical coordinates r and z) may be controlled by applying a 3-D AC trapping field potential to the electrode structure of the ion trap. The driving frequency of the trapping voltage typically falls within a range associated with the radio frequency (RF) spectrum. In the 2-D case, the radial excursions of ions along the x-y plane may be controlled by applying a 2-D AC (RF) trapping field potential between opposing pairs of electrodes. Additionally in the 2-D case, the axial excursions of ions, or the motion of ions along the central z-axis, may be controlled by applying an axial DC barrier potential between the axial ends of the electrodes. The impressing of the RF trapping voltage between the appropriate electrodes of the ion trap generates a quadrupolar electrical field that is symmetrical about the center of the 3-D ion trap or the central axis of the 2-D ion trap. The amplitude and frequency of the RF trapping voltage may be set such that ions of a desired range of mass-to-charge (m/z) ratios are constrained to orbits focused about the 3-D center or the 2-D central axis.
In addition to the RF trapping field, auxiliary or supplemental AC (which may also be RF) dipolar or quadrupolar excitation fields may be applied between at least one opposing pair of electrodes in either a 3-D or 2-D ion trap to increase the amplitudes of oscillation of ions of selected m/z ratios along the axis of that electrode pair. A supplemental AC field may be applied to increase the kinetic energies of ions for various purposes, including ion ejection and collision-induced dissociation (CID), also termed collision-activated dissociation (CAD). The supplemental AC field is typically applied so as to create a resonance condition in the ion trap at which an ion of a given m/z ratio efficiently takes up energy from the supplemental AC field. The resonance condition occurs when the secular frequency of the oscillation of an ion, in the direction of the axis along which the supplemental AC voltage is applied, matches the frequency of the applied supplemental AC voltage. The frequency of the supplemental AC voltage is typically set to about one-half or less of the frequency of the RF trapping voltage, and the amplitude of the supplemental AC voltage is typically set to a small percentage of the RF trapping voltage. Because the secular frequency of an ion of a given m/z ratio depends on the amplitude and frequency of the RF trapping voltage, the RF trapping voltage may be adjusted to bring that ion into resonance with the supplemental AC field. As an example, the RF trapping voltage may be set to 300 V at a driving frequency of 1.05 MHz, while the supplemental AC voltage may be set to 3.0 V at a resonant frequency of 485 kHz. The RF trapping voltage may then be scanned to shift the respective secular frequencies of ions of successive m/z ratios into equality with the 485-kHz frequency of the supplemental AC voltage, whereby the different ions become resonantly excited in mass-wise succession. Alternatively, instead of scanning the secular frequency of the ion to match up with a fixed-frequency supplemental AC voltage, the RF trapping voltage may be held constant while the frequency of the supplemental AC voltage is swept to the point where the resonance condition is fulfilled. Hence, ions of differing m/z ratios may be resonated in succession by ramping (or scanning) the amplitude or frequency of the RF trapping voltage or the frequency of the supplemental AC voltage.
Generally, a smaller supplemental AC voltage amplitude is utilized to excite ions for CID, whereby the amplitude of oscillation of the ions is increased enough to cause collisions with background gas molecules and consequently fragment or dissociate the ions into lower-mass species, but not enough to cause the ions to overcome the restoring forces imparted by the RF trapping field and be lost (e.g., by striking an electrode or being ejected from the ion trap). A supplemental AC voltage of greater amplitude (but still a small percentage of the RF trapping voltage amplitude) is utilized to excite ions enough to resonantly eject them from the ion trap. Thus, achieving high-efficiency CID conventionally has required a careful balancing of ion kinetic energy uptake so that the internal energy of a precursor ion accumulates sufficiently to cause dissociation while ejection of the precursor ions and fragment ions is prevented.
Ions present in the interior space of the electrode set are responsive to, and their motions influenced by, all electric fields active within the interior space. These fields include fields applied intentionally by electrical means as in the case of the above-noted AC (and optionally DC) fields, and fields mechanically (physically) generated due to the physical/geometric features of the electrode set. The mechanically generated fields may or may not be intentional and, depending on the mode of operation of the ion trap, may or may not be desirable or optimal. Both applied fields and mechanically generated fields are governed by the configuration (profile, geometry, features, and the like) of the inside surfaces of the electrodes exposed to the interior space. Points on the inside surfaces closest to the central axis, such as the apex of a hyperbolic end cap electrode (3-D case), or the apical line of a hyperbolic ring electrode (3-D case) or an elongated electrode (2-D case), have the greatest influence on an RF trapping field and thus on the ions constrained by the RF trapping field to the volume around the 3-D center or 2-D central axis of the interior of the ion trap.
In an ideal case, the 3-D or 2-D RF trapping field is purely quadrupolar. In a pure quadrupolar RF trapping field, no higher-order multipole fields are present and the secular frequency of oscillation of an ion in a given coordinate direction is independent of the secular frequency of oscillation in an orthogonal coordinate direction. The ion's secular frequency is also independent of the amplitude of the ion's oscillation. Moreover, the strength of the ideal quadrupolar field increases linearly with distance from the center of a 3-D ion trap, or from the central axis of a 2-D ion trap along either the x-axis or the y-axis. The electrodes of many conventional ion traps are hyperbolically shaped and spaced from each other so as to approach the ideal case as close as possible and thus minimize distortions in the quadrupolar field caused by multipole moments. The use of a pure quadrupolar trapping field simplifies the ejection of ions from the ion trap. This is because in the symmetrical quadrupolar case, increasing the motion of an ion in one component direction does not affect the motion of the ion in an orthogonal direction. Thus, a supplemental AC dipole may be utilized to eject an ion only along the axis of the opposing end caps of a 3-D electrode structure or along the axis between one pair of opposing elongated electrodes of a 2-D electrode structure.
On the other hand, in a trapping field consisting of a quadrupolar field that is distorted by the superposition of a multipole field, the motion of an ion in one direction may be coupled to the motion of the ion in an orthogonal direction. Moreover, the secular frequency of the ion in a combined field consisting of both quadrupolar and higher-order multipole components becomes a function of the position of the ion in the ion trap. As the amplitude of an ion's oscillation increases in response to the resonance condition promoted by the supplemental AC field, the presence of a higher-order multipole may cause the ion to shift out of resonance, thereby complicating the use of resonance excitation techniques. Thus, significant multipoles in the trapping field are typically avoided, although some recently developed techniques deliberately take advantage of the nonlinear resonance conditions enabled by multipoles. See, e.g., U.S. Pat. No. 7,034,293, commonly assigned to the assignee of the present disclosure.
In a known method for carrying out CID, an RF trapping voltage is applied to a 3-D ion trap to trap stable ions. Then all ions outside of a desired mass or mass range are expelled from the electrode structure by implementing an isolation technique. The isolated ions having the selected m/z ratio (a precursor or parent ion) are then dissociated. For example, a supplemental AC dipole voltage may be applied to the end caps at a supplemental frequency that matches the secular frequency of the ion mass of interest corresponding to motion of that ion along the z-axis, i.e., the axis along which the end caps lie and the dipole is imposed. The matching of the supplemental excitation frequency with the secular frequency creates a resonance condition, by which the ion of interest efficiently picks up energy and collides with molecules of a background gas, thereby fragmenting into product (e.g., daughter) ions. The operating parameters of the RF trapping voltage are selected such that the product ions are retained in the ion trap. The amplitude of the RF trapping voltage is then scanned (ramped up) to eject product ions in mass-wise succession from the ion trap along the axis of the end caps (e.g., z-axis). The detection of the ejected product ions enables the generation of a mass spectrum. An example of this technique is described in U.S. Pat. No. 4,736,101.
One problem with this technique is that, generally, the secular frequency of a given ion of interest cannot be precisely determined in advance. Thus, the technique is unable to deliver consistent CID performance. In addition, the supplemental AC voltage needs to be optimized individually for different ions of interest because the energy required for CID depends on the particular compound (chemical structure) to be fragmented.
Another method for carrying out CID is described in U.S. Pat. No. 5,302,826 (“the '826 Patent”), commonly assigned to the assignee of the present disclosure. As taught in the '826 Patent, after isolating a precursor (parent) ion of interest, a supplemental AC excitation voltage is applied in combination with a low-frequency (e.g., 500 Hz) signal during the CID stage. The low-frequency signal modulates the amplitude of the applied RF trapping voltage. As a result, ion secular frequency matches up with the supplemental excitation frequency periodically. In this manner, the exact supplemental excitation frequency required for CID need not be known. However, the amplitude of the supplemental excitation voltage still needs to be optimized for individual ions of interest.
In another method for carrying out CID via resonance excitation, described in U.S. Pat. No. 6,124,591, the amplitude of the excitation voltage applied to the ion trap is linearly related to the m/z ratio of the ion to be fragmented for a particular ion trap instrument. A calibration process is employed to calibrate the linear relationship on a per instrument basis. However, the amplitude of the supplemental excitation voltage still needs to be optimized for individual ions of interest if their chemical structures are different from that of the ion of the calibrant compound upon which the calibration was based.
Another method for carrying out CID via resonance excitation, described in U.S. Pat. No. 6,410,913, addresses the chemical compound dependence of CID energy required for a particular experiment by ramping the amplitude of a supplemental broadband waveform that consists of a mixture of multiple discrete frequencies. This method does not require optimization of the applied waveform amplitude for different chemical compounds. However, the broadband waveform may break or eject product (daughter) ions whose masses are close to the precursor (parent) ions, resulting in loss of information. In addition, the CID time is restricted to being the integer times of the repeat cycle of the waveform.
Another method is referred to as Red-Shifted Off-Resonance Large-Amplitude Excitation (RSORLAE) in Qin & Chait, “Matrix-Assisted Laser Desorption Ion Trap Mass Spectrometry: Efficient Isolation and Effective Fragmentation of Peptide Ions,” Anal. Chem. 1996, vol. 68, p. 2108-2112. After isolating a precursor ion, a “jump scan” is performed in which the amplitude of the applied RF trapping field is raised from a low level to a higher level over a period of 10 ms. The amplitude of the RF trapping field is then dropped abruptly to a lower level in preparation for excitation of the precursor ion. During the excitation period, the precursor ion is not excited resonantly. Instead, an AC excitation field is applied at a large amplitude (21 Vp-p) and at a frequency red-shifted about 5%, i.e., shifted to the red of the resonant frequency. This method, however, while yielding promising results for peptide ions, is not suitable for a wide range of differing compounds and chemical structures.
U.S. Pat. No. 5,451,782 describes a method for ejecting ions from an ion trap by employing a supplemental AC field having an off-resonance frequency instead of a resonance frequency. The off-resonance frequency is stated as nearly matching the resonance frequency. The amplitude of the supplemental AC field is set to a sufficiently large value to cause ions to be ejected from the ion trap without undergoing resonance excitation. This patent, however, does not teach or enable how an off-resonance waveform could be employed to successfully effect CID. Furthermore, this patent does not teach or appreciate the use of a multipole field in combination with a quadrupole field and an off-resonance waveform for any purpose or advantage.
Therefore, there is a need for providing improved methods and apparatus for exciting ions in an ion trap, particularly for effecting CID. There is also a need for providing a CID technique that may be implemented in a consistent and repeatable manner for a wide variety of ions regardless of chemical structure.